The immunological basis for the pathogenesis of rheumatic fever is generally accepted, but the detailed mechanisms are not clear. Studies are being extended to determine the degree and duration of specific lymphocyte reactivity to streptococcal antigens in rheumatic fever patients as compared to nephritics and controls. Our initial data suggest that rheumatics respond primarily to antigens from streptococcal strains isolated and associated with the disease and not to antigens associated with nephritogenic strains. To further clarify this observation, various antigenic extracts from different strains are being tested. Further studies on the immunogenetics of rheumatic fever are being carried out with typing of rheumatics, nephritics, controls and their families for B-alloantigens. A high degree of correlation with a new antisera, 6623, has been made with rheumatics from Bogota, Colombia and the New York area. This is being extended to the relatively closed and racially distinct population in Trinidad. The protein of MN 48,000 found recently to be excreted by streptoccal strains associated with nephritis will be purified in larger quantities for further characterization and development of an RIA system to detect antibodies to this protein in nephritis. Immune complexes found in large amounts in poststreptococcal sequelae and especially nephritis will be examined for the presence of this material.